1. Field of the Invention
The present invention relates to an apparatus for freeze-drying various products.
2. Description of Related Art
To work effectively in demanding environments (e.g., in the preparation of medicines that must be carefully handled under sterile conditions), apparatus protecting a product to be freeze dried must allow moisture vapor to escape while protecting against contamination of the product during the processing. Additionally, the apparatus should be fully sealable and capable of withstanding the rigors of the freeze-drying environment (e.g., chemical and temperature compatibility, etc.). Finally, all product contact surfaces of the apparatus should be appropriate and compatible for this intended use, such as, biocompatible for contact with pharmaceuticals as well as inert to prevent drug interaction.
Many freeze-drying processes involve placing open containers of material in a freeze-dryer. Containers are kept open until the freeze-drying process is completed, allowing a path for water vapor to be removed from the product. This practice, however, presents a risk of contamination that requires cleanliness and sterility of the freeze-drying equipment and the area surrounding it.
Cross contamination between different batches of product being dried at the same time is also a problem. Cross contamination has been shown to occur in 20 to 80% of vials in a freeze-dryer as reported by Barbaree and Sanchez, 26 Developments in Industrial Microbiology, Chapter 27 (1985). Freeze-drying equipment is expensive, and freeze-drying cycles are generally very long, consuming many hours or even several days for the processing of a single batch of material. As a result, freeze-drying manufacturers would prefer to maximize the use of their capital investment in the equipment by attempting to fully load the freeze-drying chamber every time it is cycled. This would result in the practice of freeze-drying different materials in the same chamber at the same time. Since all the materials are in open containers, cross contamination of product would occur. Because of the cross contamination and incompatibility of certain products, freeze-driers are thereby run only partially full, which increases costs.
One example of how to reduce the contamination risk is described in U.S. Pat. No. 3,454,178 to Bender, et al. In that patent, a device is disclosed comprising a vial and a slotted vial cap. When the vial cap is in an "up" position, it allows a path for water vapor to escape the vial. Vials are introduced into the process with their caps in the "up" position, and remain that way until the drying cycle is complete. At the end of the cycle, freeze-drier shelves squeeze down on the vials and press the caps into the "down" position, thus sealing the vials before the drier door is opened. This approach assures that contents of the vials are not contaminated after the process is complete. It also assures that water vapor cannot enter the vials and rehydrate the product once the drier doors are open; indeed, the vials are often repressurized at the end of the process with a dry inert gas, such as nitrogen, prior to pushing the vial caps into the "down" position, to maximize the shelf life of the freeze-dried product. Unfortunately, the problem of contamination of the vial contents when the vials are being loaded into the drier or during the freeze-dry process itself is not addressed by this patent.
In European Patent Application No. 343,596 to Bergmann, et al., a container is described to protect freeze-dried products from contamination during the freeze-drying process. The container has at least one side that includes a hydrophobic, porous, germ-tight, water vapor-permeable membrane. Water vapor can escape the closed container through this porous membrane, while the membrane represents a barrier to contamination. Another technique used involves freeze-drying material in a container that has a porous hydrophobic wall. An example of this approach is taught in U.S. Pat. No. 5,309,649 to Bergmann. Neither of these approaches, however, addresses the concern about rehydrating the contents of the container once the doors of the drier are opened. It is not clear how products freeze-dried in such a container could be kept dry and finally packaged in a vapor-tight container without first exposing the dried product to humidity. Thus, a need exists for a container for freeze-dried products that maintains a well-defined level of protection throughout the entire drying process, as well as providing means for forming a vapor-tight seal on the container before the dryer doors are open.
It has been suggested to use an open-cell foamed hydrophobic porous membrane for drying pasty high viscous compositions in U.S. Pat. No. 5,164,139 to Fujioka et al. This patent suggests using a polytetrafluoroethylene (PTFE) membrane as a product wrap in such an application. While this approach may work under the described conditions, freeze-drying in this manner is not particularly suitable for many freeze-drying processes where the material is left in a container or must be transferred to another container without contamination after the freeze-drying process.
Another approach is described in co-pending U.S. patent application Ser. No. 08/292,992 filed Aug. 19, 1994, by C. Bradford Jones. In that application, a vented vial is provided that utilizes a stopper employing a vent made from permeable PTFE membrane. The porous venting media provides a barrier to bacteria and particulate contamination while permitting the passage of gases, such as air and water vapor. The product described in the copending patent application provides inherent improvements over existing technology insofar as chemical inertness of the stopper material. Regretfully, for some applications the stopper may not adequately combine barrier properties with sufficient chemical compatibility and other desirable properties, such as lubricity, sealing, and venting.